Endocrinology of ageing Flashcards
Age: nutritional status
Weight
- increased from mid 30s
Lean body mass
- decrease 6-8%/ decrease from mid 30s
Diet
- trend towards decreased intake total energy and protein with increase age
Age: insulin/ glucose
Increased [insulin] and [glucose] with age
- increased insulin resistance
- decreased peripheral glucose uptake
Increased prevalence metabolic syndrome with increase age
Menopause
Ovarian failure
Oestrogen levels
- pre-menopausal: cycling
- post menopausal: very low constant levels
Age at menopause around 50
Symptoms of menopause
Hot flushes, night sweats
Median duration of menopause symptoms 7 years
Morbidity of menopause
Increase osteoporosis
Increase CHD
Increase sexual dysfunction
Post menopausal HRT
Inital observational studies showed benefits
Some subsequent RCTs showed no benefits and increased risks
However risk: benefit ratio depends on
- other risk factors
- age of woman and duration of HRT use
- types of HRT
Post menopausal HRT benefits
Rx menopausal Sx
Decreased osteoporosis/ fracture risk
Post menopausal HRT risks
Increased venous thrombo-embolism
Increased breast Ca (small)
Increased endometrial Ca
Male gonadal axis
Gradual decrease [testosterone] with increase in age
Wide range of normality at all ages
At 75 years, mean [testosterone] 2/3rd that of a 25 year old
Poor association between libido/ erectile dysfunction and [testosterone]
Clinical hypogonadism
Decreased sexual function
Increased osteoporosis
Decreased muscle strength
Testosterone treatment; bones
Increased bone mineral density if hypogonadal
Bisphosphates work, independent of androgen status
Testosterone treatment: body composition
Increase lean body mass
Decrease fat mass
No convincing functional benefits demonstrated
Increased muscle strength with supra physiological doses
Risks of testosterone treatment
Prostate (benign prostatic hypertrophy/ cancer)
Erythropoeisis
Possible cardiovascular risk
Potential risks of GH treatment
Increased cancer: increase [IGF-I] in observational studies is associated with increased risk non smoking related cancer
- prostate, colon, breast
Increased T2 DM
Side effects
- soft tissue oedema
- arthralgias
- carpal tunnel syndrome
Age: cortisol
Increase trough levels cortisol with increase age
Phase advance of diurnal rhythm
Cortisol: sapolsky’s glucocorticoid cascade hypothesis
Decreased hippocampal glucocorticoid and mineralocorticoid receptors
Decreased sensitivity to glucocorticoid negative feedback
Increased [glucocorticoids]
Hippocampal neurons vulnerable to damage
Importance of DHEA in men
Overwhelming excess of more potent circulating androgens
Contribution to androgenic effects in men ‘modest’ at most
Decrease in [DHEA] with age
By 70-80 years [DHEA] around 5-10% of peak
Observational studies have suggested increase in [DHEA] associated with
- increase QOL, increase bone mineral density
- decrease in cognitive decline, decrease in coronary heart disease
Decrease [DHEA] is a non specific marker of ill health
- associations may not be causal
Age: thyroid function
Slight increase in [TSH] with age
Decrease in peripheral T4 -> T3 conversion with age
Decrease in [T3] with age
No evidence for beneficial effect of T4 treatment
Starvation/ AN: insulin, glucose and leptin
Decrease insulin and glucose and increase insulin sensitivity
Leptin
- produced by white adipose tissue
- reports nutritional information to the hypothalamus
- decrease leptin leads to increased food intake, decreased energy expenditure and decreased fertility
Starvation/ AN: oestrogen/ testosterone
Decrease LH and FSH
Decrease oestrogen and testosterone
Decreased fertility, amenorrhoea
- hypothalamic amenorrhoea
Osteoporosis
Central mediator: kisspeptin
A GnRH secretagogue
KISS1 neurons highly responsive to oestrogen, implicated in both positive and negative feedback of sex steroids on GnRH production
Metabolic influences o reproduction mediated by leptin via the kisspeptin system
Starvation/ AN: GH/ IGF axis
GH resistance
- increase GH and decrease IGF-I
Seen in acute starvation and in AN
Down regulation of hepatic GH receptor and/ or post receptor defect
Reversible with re-feeding
Starvation/ AN: thyroid function
TSH and T4 lower limit of normal
Decreased T4 conversion to T3 leads to less T3 (active)
Increase T4 conversion to rT3 leads to increase rT£ (inactive)
Consequences
- lower basal metabolic rate
- conserve energy
